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However, the merits of broadly targeting S versus focusing antibody onto the smaller receptor binding domain (RBD) are unclear. Here we assess prototypic S and RBD subunit vaccines in homologous or heterologous prime-boost regimens in mice and non-human primates. We find S is highly immunogenic in mice, while the comparatively poor immunogenicity of RBD is associated with limiting germinal centre and T follicular helper cell activity. Boosting S-primed mice with either S or RBD significantly augments neutralising titres, with RBD-focussing driving moderate improvement in serum neutralisation. In contrast, both S and RBD vaccines are comparably immunogenic in macaques, eliciting serological neutralising activity that generally exceed levels in convalescent humans. These studies confirm recombinant S proteins as promising vaccine candidates and highlight multiple pathways to achieving potent serological neutralisation.<\/jats:p>","DOI":"10.1038\/s41467-021-21665-8","type":"journal-article","created":{"date-parts":[[2021,3,3]],"date-time":"2021-03-03T11:09:58Z","timestamp":1614769798000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":82,"title":["Immunogenicity of prime-boost protein subunit vaccine strategies against SARS-CoV-2 in mice and macaques"],"prefix":"10.1038","volume":"12","author":[{"given":"Hyon-Xhi","family":"Tan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9072-1017","authenticated-orcid":false,"given":"Jennifer A.","family":"Juno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7285-4054","authenticated-orcid":false,"given":"Wen Shi","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7892-6802","authenticated-orcid":false,"given":"Isaac","family":"Barber-Axthelm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah G.","family":"Kelly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen M.","family":"Wragg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7091-0048","authenticated-orcid":false,"given":"Robyn","family":"Esterbauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thakshila","family":"Amarasena","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3754-2642","authenticated-orcid":false,"given":"Francesca L.","family":"Mordant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1713-3056","authenticated-orcid":false,"given":"Kanta","family":"Subbarao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8539-4891","authenticated-orcid":false,"given":"Stephen J.","family":"Kent","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5593-9387","authenticated-orcid":false,"given":"Adam K.","family":"Wheatley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,3,3]]},"reference":[{"key":"21665_CR1","doi-asserted-by":"publisher","first-page":"818","DOI":"10.1126\/science.abc5343","volume":"369","author":"W Deng","year":"2020","unstructured":"Deng, W. et al. 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